Mass Spectrometry Topical Group Meetings

(Past Event)

Oct 18, 2017 – MSDG Meeting

The NJ Mass Spectrometry Discussion Group is pleased to announce our October Monthly Meeting.NJ MSDG is the second largest mass spectrometry professional association in the nation behind ASMS, with over 1,100 members in the tristate area. [ homepage ]

Mass spectrometry has become an essential tool for all stages of drug discovery and development. Similarly, mass spectrometry has broad utility in studies of the safety and efficacy of botanical dietary supplements. These applications to botanical dietary supplements include studies of the mechanisms of action (target identification and validation); identification of active natural products (drug discovery); studies of metabolism of active compounds; investigation of the potential for drug-botanical interactions (similar to studies of drug-drug interactions); and investigation of the pharmacokinetics of active compounds. Mass spectrometry is also being used in support of Phase I, II and III clinical trials of safety and efficacy of botanical dietary supplements. Preclinical and clinical examples will be drawn from studies of botanical dietary supplements such as red clover, black cohosh, hops, and licorice that are being used by menopausal women as alternatives to conventional hormone therapy.

Supercritical fluids have desirable properties like high density, low viscosity, and high diffusivity, which make them suitable mobile phases for supercritical fluid chromatography (SFC), an analytical technique that is amenable to high-throughput, high-resolution analysis. We attempted to apply SFC/MS to metabolic profiling. Furthermore, we tried to expand the range of applications of SFC for diverse compounds, including polar compounds. Additionally, we have developed supercritical fluid extraction (SFE) technologies for metabolic profiling. SFE can be used to extract labile compounds without degradation or loss. We applied SFE to the extraction of various metabolites and combined it with online SFC/MS for metabolic profiling. Furthermore, we developed a new online SFE-SFC-MS instrument.

Tue Sep 12, 2017 – MSDG Symposium, Poster & Vendor Show

NJ MSDG is the second largest mass spectrometry professional association in the nation behind ASMS, with over 1,100 members in the tristate area. [ homepage ]

We had a fantastic turn out for our last year’s vendor show (~250 attendees) with guest lectures.

This year, we are pleased to announce that Professor Scott McLuckey, from Purdue University, will be one of our guest lecturer. The other presentation will be given by Professor Brian Chait of The Rockefeller University.

Abstract: We have been developing approaches to exploit the unique geometry of the linear electrostatic ion trap (ELIT) for general purpose mass spectrometry and tandem mass spectrometry. This effort has involved the implementation of ion isolation and ion activation methods along with optimization of mass analysis. A synopsis on our current status will be provided along with a detailed comparison of two complementary approaches to mass analysis that are capable of being executed simultaneously in the ELIT. One approach involves the detection of ions via image current measurement with subsequent Fourier transformation of the time-domain signal. We refer to this approach as FT-ELIT MS. Alternatively, ions can be detected after a fixed storage time via an externally mounted channelplate detector. We refer to this approach as multi-reflection time-of-flight (MR-TOF) MS. Both approaches can be used on the same ion population because the detection approaches are independent and do not interfere with one another. Based on the inherent characteristics of the two approaches, they exhibit advantages and disadvantages relative to one another, depending upon the needs of the measurement. As a result, they tend to be complementary. Currently, the FT-ELIT approach in our apparatus is capable of achieving mass resolution in excess of 100,000 FWHM at m/z 176. However, MR-TOF experiment achieves high resolution in a shorter period of time at the expense of mass range. These differences are illustrated and discussed at a fundamental level and musings on how they might be used in concert will be discussed.

Bio: Scott A. McLuckey received his B.S. in Chemistry at Westminster College (New Wilmington, PA) in 1978 and doctorate in Analytical Chemistry at Purdue University (West Lafayette, IN) in 1982. He then served as a Postdoctoral Fellow at the FOM Institute for Atomic and Molecular Physics (Amsterdam, The Netherlands) until late 1983. He was then awarded a Wigner Fellowship at Oak Ridge National Laboratory in the Analytical Chemistry Division. While at Oak Ridge, he served in such capacities as Group Leader, Organic and Biological Mass Spectrometry, and Head of Analytical Spectroscopy Section within the Chemical Sciences Division. In 2000, he moved to Purdue University as Professor of Chemistry. In June 2008, he was named the John A. Leighty Distinguished Professor of Chemistry at Purdue.

McLuckey’s research emphases have been placed in the areas of gas-phase ion chemistry and instrumentation for organic and biological mass spectrometry. Fundamental aspects of ionization, unimolecular reactions, and bi-molecular reactions have been studied with the goal of improving the capabilities of analytical mass spectrometry. Ion activation, ion/molecule reactions, and ion/ion reactions have been major focal areas within the context of the mass spectrometry/mass spectrometry experiment. Instrumentation for tandem mass spectrometry has also been highlighted with emphasis on electrodynamic ion traps and ion trap/hybrid instruments. This research, performed in conjunction with colleagues and post-docs at ORNL, students and post-docs at Purdue, and other collaborators, has been described in roughly 350 papers appearing in the peer-reviewed literature. He has been awarded eleven U.S. Patents on various technologies associated with mass spectrometry. The major current areas of emphasis are the identification and characterization of macro-molecules, primarily via whole molecule tandem mass spectrometry, ion/ion reaction chemistry, and the development of electrostatic ion traps for tandem mass spectrometry. Recognition for the work has included the Biemann Medal, Hites Award, and Distinguished Contribution Award from the American Society for Mass Spectrometry (ASMS), The Curt Brunneé Prize (2000) and Thomson Medal (2016) from the International Mass Spectrometry Foundation, and the Division of Analytical Chemistry Chemical Instrumentation Award and Field and Franklin Award in Mass Spectrometry from the American Chemical Society

McLuckey served as an editor of the International Journal of Mass Spectrometry from January, 1978 through December, 2016 and currently serves as an Associate Editor of Analytical Chemistry. He has co-taught short courses at the annual ASMS Conference on Fundamental Aspects of Mass Spectrometry (3 years) and Quadrupole Ion Traps (6 years). He served as VP for Programs, President, and Past-President of the ASMS from July, 2008-June 2014. He currently serves on the executive board of the International Mass Spectrometry Foundation as the North American Regional Representative.

Abstract: The myriad events that occur in living cells (replication, organellar assembly, transport, genome organization, transcription etc.) are to a large extent carried out through dynamic associations and assemblies of macromolecules. I will describe our efforts to develop and integrate sets of tools that are designed to throw light on the evolution, structure and function of these macromolecular machines.

To do this, we are developing approaches for elucidating proximal, distal, and transient protein-protein interactions in cellular milieus, as well as for determining distance restraints between amino acid residues within large protein assemblies by chemical cross-linking and mass spectrometry. The long-term goal of this research is to develop what I will loosely term a “molecular microscope” for defining cellular systems with scales spanning all the way from dimensions of the cell to atomic resolution of molecules.

Bio: Brian T. Chait was born in Cape Town, South Africa. He received his B. Sc. (1969) and B. Sc. (Hons) (1970) from the University of Cape Town and D.Phil. (1976) in experimental nuclear physics from Oxford University. He has spent the past 38 years at The Rockefeller University, where he is currently Camille and Henry Dreyfus Professor, heads the Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, and directs the NIH-funded National Resource for the Mass spectrometric Analysis of Biological Macromolecules, constructing novel mass spectrometers, developing useful methodologies, and applying the developed technologies to challenging biological and biomedical problems. This work is documented in 392 research papers and 31 US patents, many of which are commercialized and widely used throughout the world. These publications have been cited 48,000 times, with an average citation rate of 122 citations/paper. Professor Chait has received several awards for his research in developing instrumentation and methods for characterizing proteins, including the 2000 Bijvoet Medal, the 2002 ACS Field & Franklin Award for Outstanding Achievement in Mass Spectrometry, the 2007 HUPO 2007 Distinguished Discovery Award In Proteomics, the 2012 Per Edman Award, and the 2015 ASMS Award for a Distinguished Contribution in Mass Spectrometry.

Jun 28, 2017 – MSDG Meeting

The NJ Mass Spectrometry Discussion Group is pleased to announce our June Monthly Meeting.NJ MSDG is the second largest mass spectrometry professional association in the nation behind ASMS, with over 1,100 members in the tristate area. [ homepage ]

A different approach to electrospray LC/MS using flow-based ion transport in to the mass spectrometer better resists changes in performance due to contamination. Using the flow of the nebulizing gas to entrain ions in to the system eliminates the need for a high voltage ion funnel or charged capillary and eliminates a number of parameters such as desolvation potential. The result is better long term stability, sensitivity, fewer variables and much lower maintenance. This is especially evident with more challenging sample matrices. The talk includes relevant application examples that demonstrate this principle and other benefits of the design.Bio:Mark Greenbaum has been associated with analytical chemistry and the analytical instruments industry for over 30 years. He has been involved in LC/MS, liquid chromatography, atomic force microscopy, scientific software and others. He worked with the inventors of the QSight LC triple quad and came to PerkinElmer with the acquisition of the technology. His most recent work representing QSight makes him uniquely qualified to speak about the system, its use and LC-MS/MS. Mark received his degree from the University of Maryland.

Jon Sims is a career chemist and recognized expert in trace metals analysis. Jon’s ability as a Technical Advisor will enhance and support comprehensive solutions for the new USP (U.S. Pharmacopeia) <232><233><2232> regulations. Jon is a recently retired analytical manager from pharmaceutical giant GlaxoSmithKline, where he helped develop and implement strategies for ICH (International Conference on Harmonization) Q3D, USP <232>. He holds a BSc (Honors)in Chemistry from Loughborough University. He is also a member of the Royal Society of Chemistry, Association for Laboratory Automation, and acts as a referee for the Journal of Pharmaceutical Sciences.

May 10, 2017 – MSDG Meeting

The NJ Mass Spectrometry Discussion Group is pleased to announce our MayMonthly Meeting.NJ MSDG is the second largest mass spectrometry professional association in the nation behind ASMS, with over 1,100 members in the tristate area. [ homepage ]

Early analytical profiling has become an integral component in biologics discovery & development. This presentation will highlight the impact of applying ultra-high resolution mass spectrometry to facilitate selection and engineering of biologics leads. Approaches to minimize risks associated with chemical degradation and other biophysical properties will be discussed.

Attendees of this technology seminar will hear about the latest advancements in ultrahigh-resolution time-of-flight hardware and their application to the analytical challenges facing innovators and biosimilars characterization labs. Innovations in hardware, software and application-specific workflows will be highlighted. In particular, the use of MALDI- and LC-TOF hardware in combination, all acquired and visualized with a single, ease-to-use, 21CFR Part 11 compliant software package; Biopharma Compass 2.0. Several case studies involving monoclonal antibodies characterization will be presented to highlight: How high-confidence (high resolution) intact/subunit workflows improves labs productivity and; how automation of routine data processing tasks improves the system utilization time.

The X500B QTOF is a new instrument and software solution that improves robustness and reliability, reduces complexity and streamlines analysis workflows so that everyone using the instrument can get expert results. It is the first true benchtop, high-resolution mass spectrometer purpose-built for biologics characterization. Combining intuitive and powerful new software tools with a robust, reliable, and compact instrument, the X500B system is specifically designed to make characterization tasks simpler and to get biotherapeutic characterization answers faster.

The SCIEX Biotransform Solution featuring the new MetabolitePilot 2.0 software is a powerful combination of hardware and software that will accelerate MetID by providing automated metabolite structure generation and a dedicated workflow for peptides and ADCs. Featuring SWATH data-independent acquisition on either the TripleTOF 6600 system or X500 QTOF system, the SCIEX Biotransform Solution ensures consistent and reproducible MS/MS are collected for all detectable species, resulting in reliable detection and identification from a single injection. With brand new workflows for peptides and ADCs and multiple peak finding strategies utilizing MS and MS/MS information MetabolitePilot 2.0 software is specifically designed to make MetID for these complex molecules simpler and easier.

Since the introduction of the first recombinant DNA-derived protein insulin in the 1980s and the launch of Interferons and Interleukins in the 1990s, biologics market has shown a healthy growth. This is largely due to advances in recombinant DNA technology that have provided the means to produce therapeutic proteins. Mass spectrometry is uniquely positioned to cope with additional challenges for the analysis of biologics, due to its analytical sensitivity and specificity. This presentation will present current status and trends in MS characterization of biologics, including primary structural analysis and higher order structure characterization.

High resolution analytical technologies are moving out of the realm of characterization and into the regulated environments of late development, manufacturing and QC organizations. Analytical managers are now challenged to not only develop an effective characterization strategy, but participate in the lifecycle planning of those assays as they evolve into attribute monitoring, and validated release assays for a commercial product. Harmonization of platforms across these organizations has remained a challenge to this process, but the development of platforms for both high resolution and routine nominal mass detection that can be deployed across an entire organization have fueled great interest progressing LCMS analysis later in development and into QC organizations. While peptide-centric monitoring of multiple product variants has recently generated great interest and concerns, there is already a progression of developing and validating intact/subunit mass profiling QC release assays. In this seminar, we will discuss the benefits of applying the HRMS QTof platform under UNIFI for comprehensive primary structural characterization in support discovery and development efforts, transitioning this platform into regulated late development with a mix of targeted monitoring and new variant identification workflow, and multiple strategies at the intact/subunit mass and peptide map level for effective deployment of critical assays into a QC-lot release environment.

Sep 13, 2016 – MSDG Symposium & Vendor Show

NJ MSDG is the second largest mass spectrometry professional association in the nation behind ASMS, with over 1,100 members in the tristate area. [ homepage ]

We had a fantastic turn out for our last year’s vendor show (~250 attendees) with guest lectures given by luminaries such as Professor Tom Baillie (former VP of Drug Metabolism and Pharmacokinetics at Merck and currently Dean Emeritus at University of Washington School of Pharmacy), and Professor Richard Capprioli (Stanford Moore Chair in Biochemistry and Director of the Mass Spectrometry Research Center at Vanderbilt University School of Medicine).

This year, we are pleased to announce that Professor David Muddiman, from North Carolina State University, will be one of our guest lecturer. The other presentation will be given by Dr. Wilson Shou of Bristol-Myers Squibb Co.

Program

2:30 – 8:00 PM Vendor Show

2:30 – 3:00 PM Vendor Set Up – Hotel Ballroom

3:00 – 4:00 PM Registration – Hotel Ballroom

4:15 – 4:45 PM Cocktail Break / vendor interaction

4:45 – 5:45 PM Presentation by Professor David Muddiman (North Carolina State University) Title: Working Around the Cluck: A Systems Biology Approach to Understanding the Origin and Biology of Ovarian Cancer.

Mass spectrometry offers the most robust platform to discover and characterize new diagnostic, prognostic, and therapeutic biomarkers for ovarian cancer across all molecular classes. Moreover, a systems biology approach will allow the underlying biology and origin of ovarian cancer to be understood. This presentation will discuss the challenges specific to the study of epithelial ovarian cancer (EOC) in humans and how these challenges have directed our thinking in terms of the development of model organisms and mass spectrometry-based bioanalytical strategies. First, to augment the human model, we developed the domestic hen model of spontaneous EOC, which allowed us to longitudinally sample the rapid onset and progression of the disease in a controlled environment. Second, we developed bioanalytical tools to characterize structurally challenging analytes that are critical to a systems-level analysis. To increase the electrospray response of N-linked glycans, we synthesized novel hydrophobic tagging reagents which have the added benefit of being able to incorporate a stable-isotope label for relative quantification experiments (INLIGHTTM). Furthermore, we developed a novel ionization technique for tissue imaging of lipids and metabolites. This unique model organism has and continues to provide new insights into the biology of ovarian cancer; combined with other –OMICS data obtained through these novel bioanalytical approaches, we will understand the origin of ovarian cancer and ultimately translate that knowledge to humans.

Biography

David C. Muddiman is the Jacob and Betty Belin Distinguished Professor of Chemistry and Founder and Director of the W.M. Keck FTMS Laboratory for Human Health Research at North Carolina State University in Raleigh, NC. Prior to moving his research group to North Carolina State University, David was a Professor of Biochemistry and Molecular Biology and Founder and Director of the Mayo Proteomics Research Center at the Mayo Clinic College of Medicine in Rochester, MN. Prior to his appointment at the Mayo Clinic, David was an Associate Professor of Chemistry at Virginia Commonwealth University where he began his academic career as an assistant professor in 1997 with an adjunct appointment in the Department of Biochemistry and Molecular Biophysics where he was also a member of the Massey Cancer Center. David was born in Long Beach, CA in 1967 but spent most of his formative years in a small town in Pennsylvania. David received his B.S. in chemistry from Gannon University (Erie, PA) in 1990 and his Ph.D. in Analytical Chemistry from the University of Pittsburgh in 1995 under the auspices of David M. Hercules. He then was a Department of Energy Postdoctoral Fellow at Pacific Northwest National Laboratory in the Environmental Molecular Sciences Laboratory working with Richard D. Smith from 1995-1997. Dr. Muddiman is Editor of Analytical and Biological Chemistry and Associate Editor of the Encyclopedia of Analytical Chemistry as well as on the Editorial Advisory Board of Mass Spectrometry Reviews, Molecular and Cellular Proteomics, Rapid Communications in Mass Spectrometry, and the Journal of Chromatography B. He also serves on the advisory board of the NIH Funded Complex Carbohydrate Research Center, University of Georgia and the Yale/NIDA Neuroproteomics Center, Yale University. Dr. Muddiman served as a member of the ASMS Board of Directors and Treasurer of US-HUPO; he is currently the President of US HUPO. His group has presented over 500 invited lectures and presentations at national and international meetings including 20 plenary/keynote lectures. His group has published over 225 peer-reviewed papers and has received four US patents. He is the recipient of the 2015 ACS Award in Chemical Instrumentation, 2010 Biemann Medal, American Society for Mass Spectrometry, 2009 NCSU Alumni Outstanding Research Award, the 2004 ACS Arthur F. Findeis Award, the 1999 American Society for Mass Spectrometry Research Award, and the 1990-91 Safford Award, University of Pittsburgh, for Excellence in Teaching. Dr. Muddiman’s research directed at the development of innovative technologies, systems biology, and model organisms is funded by the National Institutes of Health, the National Science Foundation, the Department of Energy, and The United States Department of Agriculture.

Abstract:Dr. Wilson Shou

Improvements in mass spectrometry (MS)-based analytical throughput have been achieved using laser desorption ionization (LDI) techniques and this has led to increased utility for this technology amongst research groups supporting early drug discovery efforts. In particular, lead discovery teams that perform high-throughput screening (HTS) assays that are intended to identify active compounds against therapeutic targets of interest have begun to adopt this label-free methodology as an orthogonal screening approach to well-established fluoresence-based assays. Furthermore, optimization of the “hits” identified through HTS requires additional in vitro studies to assess absorption, distribution, metabolism, and elimination (ADME) properties by lead profiling groups who prefer to use native, clinically-relevant substrates. Since HTS and HT-ADME groups can generate thousands of samples on a daily basis, it is necessary to have high-throughput analytical platforms capable of processing these demands. The move towards label-free screening in drug discovery has increased the demand for mass spectrometry-based analysis, and because of this, it is important to explore new technologies aimed at improving MS-based readout speeds in order to continue to support the increasing sample volume demands of these groups.

Assays that utilize mass spectrometry for analysis are both sensitive and selective and offer the ability to provide label-free detection of physiologically relevant substrates and products. MS-based methodologies, however, have traditionally relied upon liquid chromatography (LC) or on-line solid phase extraction (SPE) as front-end sample delivery mechanisms. Because of this, they typically have slow cycle times that aren’t amenable to high throughput screening efforts. Using newer approaches that employ laser desorption techniques to directly introduce the contents of wells into the mass spectrometer, it is possible to achieve throughputs that approach those of plate-reader assays and meet the demands of early discovery screening applications. Here we investigated the approach of coupling nanoliter sample deposition with Laser Diode Thermal Desorption (LDTD) – tandem mass spectrometry (MS/MS) and evaluated its utility in providing an ultra high-throughput, label-free detection method for various applications in HTS and HT-ADME groups.

Seminar Speakers

The demand is increasing for protein detection and quantitation in biological fluids for disease detection, protein therapeutics monitoring, and drug development. Current methods use highly sensitive and specific triple quadrupole mass spectrometry (QqQ-MS) to quantify protein-digested peptides to then correlate original intact protein concentrations in the sample. This bottom-up method for protein quantitation can introduce errors. Therefore, for more accurate protein quantitation researchers use expensive isotopically labeled proteins for standards. A method that bypasses the protein digestion step to directly quantify intact proteins on QqQ-MS was developed and will be presented. Myoglobin, cytochrome c, lactalbumin, lysozyme, and ubiquitin were selected as protein standards for the proof-of-principle work. Our intact protein quantitation method was developed on a Shimadzu LCMS-8050 QqQ-MS utilizing multiple reaction monitoring (MRM). The experimental pathway and associated challenges that ultimately led to MRM transitions for all protein standards will be shown. The result was calibration curves of respectable linearity (R2>0.99). Further, in order to address complex matrices in biological fluids for future applications, a generic reversed-phase chromatography method was developed on Restek Wide Pore Viva C4, C8, C18, Biphenyl, and PFP Propyl (2.1 x 100 mm; 5 μm;300 Å) columns. Prostate specific antigen (PSA) was also included in the study to prove the feasibility of the method for both the liquid chromatography and mass spectrometry aspects. Specificity of the MRM detection was evaluated for both urine and plasma matrices. The method is envisioned to be a model for future development of targeted methods for analysis of important disease indicators such as proteins in biological fluids, especially for clinical diagnostic and treatment advancements.

II. Scott A. Kuzdzal, PhD

General Manager of Marketing, Shimadzu Scientific Instruments

Fully Integrated & Automated LC-MS/MS Sample Preparation and a Brief Introduction to other New Innovations from Shimadzu

ABSTRACT:

In clinical and pharmaceutical laboratories, time is money. Sample preparation for the detection of target analytes such as steroids and immunosuppressant drugs in serum by LC-MS/MS typically involves complex, offline extraction methods such as solid phase extraction or liquid/liquid extraction, both of which require additional sample concentration and reconstitution in appropriate solvents. These sample preparation methods are time-consuming, often taking one hour or more per sample, and are more vulnerable to variability due to errors in manual preparation. We herein present the full integration and automation of steroid and immunosuppressant assay sample preparation and LC-MS/MS analysis using an innovative, automated sample preparation instrument (CLAM-2000) coupled directly to Shimadzu ultra-fast mass spectrometry. This completely integrated, automated quantification method for immunosuppressant and steroid drug compounds allows routine analysis with high data quality/precision, reduced time, increased throughput and enhanced safety.

This talk will also introduce a new ultra-high speed LCMS system for multiplexed analyses that allows users to double the throughput of an existing method. In an analysis of four biomarker compounds for the four major molecular species in the Cytochrome P450 family, the innovative, new Nexera-MX system completed the analysis in only 38 seconds whereas conventional HPLC required one minute and twenty-two seconds.

Search this site . . .

Latest News

Message From Miriam Gulotta

Becoming the 2018 Chair of NJACS is an immense honor as well as a daunting responsibility. First, I want to thank all the people who participate in NJACS topical groups, symposia, SEED mentors/mentees, College Chapters, ... and all the other NJACS involved events. It’s you who are both the face and the strength of our section.
Read more »✎